Lead Investigator: Guoxing Wan, Hubei University of Medicine
Title of Proposal Research: Efficacy and safety of atezolizumab plus bevacizumab for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade
Vivli Data Request: 8175
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Hepatocellular carcinoma (HCC) is the fifth most common type of primary liver cancer with approximately 700,000 deaths of HCC per year worldwide, and ranks as the second and sixth leading cause of cancer death in males and females, respectively. It is well known that the condition of the liver, the quality and quantity of cells, has a substantial influence on the prognosis of HCC patients. The Child-Pugh (C-P) classification has been widely used to assess liver dysfunction. The C-P includes objective measures like albumin and bilirubin levels in the blood, as well as more subjective measures which rely on clinicians’ evaluations. As generally known, albumin is a protein that helps move many small molecules through the blood, including bilirubin. Bilirubin is a yellow substance made during the normal process when old blood cells are broken down and cleared by the liver. The albumin-bilirubin (ALBI) score based on albumin and bilirubin levels in the blood is a new model for assessing the severity of liver dysfunction, which is also a method of assessing liver failure. Most studies have demonstrated that ALBI grade is useful in guiding the treatment strategies including targeted therapy (cabozantinib, bevacizumab), immunotherapy (ipilimumab, nivolumab, pembrolizumab, atezolizumab), the destruction of cancer tissues by extreme temperatures and radiation therapy in HCC patients who were considered unresectable (where the tumor is not capable of being surgically removed). In this setting, the tumor can no longer be removed through surgery either because they already have advanced-stage HCC, or because there would be insufficient liver after surgery to carry out its functions (<40% for patients with scarring of the liver caused by long-term liver damage; <30% for patients without scarring of the liver caused by long-term liver damage) or intolerable surgical trauma. IMbrave150 is a global, open-label, randomised, phase 3 trial to evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in patients with untreated locally advanced or metastatic (where the cancer has spread to other areas of the body) hepatocellular carcinoma. The study demonstrated better outcomes for patients treated with atezolizumab plus bevacizumab. Given the impressive result of IMbrave150, atezolizumab plus bevacizumab therapy is the only cancer immunotherapy regimen currently approved by the FDA for the first-line treatment of unresectable or metastatic hepatocellular carcinoma. However, the superiority of atezolizumab plus bevacizumab in patients with different ALBI grades remains inconclusive. This study will provide new opinion based on ALBI grade when employing atezolizumab plus bevacizumab therapy, and will propose the consideration of ALBI grade-based subgroup analysis in future randomised control trials. A post-hoc analysis using the accessed data from IMbrave150 study will be performed to evaluate efficacy and safety of atezolizumab plus bevacizumab therapy compared to sorafenib monotherapy in HCC stratified by different ALBI grades.
Statistical Analysis Plan:
Atezolizumab plus bevacizumab therapy in IMbrave150 study is the only cancer immunotherapy regimen currently approved by the FDA for the first-line treatment of unresectable or metastatic hepatocellular carcinoma. Therefore, we focused on the association of ALBI grade the association of ALBI grade with efficacy and safety of first-line atezolizumab plus bevacizumab therapy. Baseline data, such as patient demographics and disease characteristics, will be summarized according to ALBI grade in immunotherapy arm and in sorafenib arm using descriptive statistics. Age will be reported as median with corresponding range and other variables will be reported as categorical variables. The clinical response will be descriptively summarized according to ALBI grade in each arm. Additionally, A post-hoc univariate and multivariate analysis was performed to evaluate the association of ALBI grade and other baseline variables with Overall Survival (OS) and Progression-Free Survival (PFS). The same Cox proportional hazard model was run independently for each treatment arm. Safety analyses in different ALBI grades were descriptive. The missing data will be excluded from the analysis.
Requested Studies:
A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Data Contributor: Roche
Study ID: NCT03434379
Sponsor ID: YO40245
Summary of Results:
We were unable to bring our analysis to completion due to that the goal of our research protocol has been achieved by the other team whom have proven the value of ALBI grade with the Phase III IMbrave150 Study and published their results. Our research may be hard to provide new insight. Although we did not complete our SAP, our findings provide support of Atezo+Bev in patients with advanced HCC in ALBI grade 1 but not ALBI grade 2.